Electrochemical Synthesis of Isoxazolines: Method and Mechanism

Abstract

An electrochemical method for the green and practical synthesis of a broad range of substituted isoxazoline cores is presented. Both aryl and more challenging alkyl aldoximes are converted to the desired isoxazoline in an electrochemically enabled regio‐ and diastereoselective reaction with electron‐deficient alkenes. Additionally, in‐situ reaction monitoring methods compatible with electrochemistry equipment have been developed in order to probe the reaction pathway. Supporting analyses from kinetic (time‐course) modelling and density functional theory support a stepwise, radical‐mediated mechanism, and discounts hypothesised involvement of closed shell [3+2] cycloaddition pathways.

Nitrile Oxide, Alkenes, Dipolar Cycloaddition, Isomerization and Metathesis Involved in the Syntheses of 2-Isoxazolines

“…Very recently, a broadly applicable electrochemical methodology for the synthesis of 3,5-disubstituted isoxazolines that is quantifiably greener than comparable non-electrochemical methods was published— Scheme 303 [ 336 ].…”

“… Electrochemical synthesis of isoxazolines from oximes and acrylates [ 336 ]. SS—stainless steel electrode, HFIP—hexafluoroisopropanol.…”

Electrochemical Synthesis of Pyrazolines and Pyrazoles via [3+2] Dipolar Cycloaddition

“…In general, the presented approach is analogous to the synthesis of isoxazoles, and isoxazolines from aldoximes [29] . The synthesis of nitriles, isoxazolines and isoxazoles can be achieved by electrolysis via nitrile oxides as key intermediates [30–34] . These reactions have been investigated since the late 1980s when Shono et al.…”

Elektrochemische Synthese von Pyrazolinen und Pyrazolen via [3+2] dipolarer Cycloaddition

“…[29] Die Synthese von Nitrilen, Isoxazolinen und Isoxazolen kann durch Elektrolyse über Nitriloxide als Schlüsselintermediate erreicht werden. [30][31][32][33][34] Diese Reaktionen werden seit den späten 1980er Jahren untersucht, als Shono et al die halogenvermittelte Synthese von Nitrilen aus Oximen veröffentlichten. [30,31] Die Verwendung von Cl À /Cl + als Mediator an Platinelektroden führt jedoch zu starker Korrosion des wertvollen Metalls.…”

“…Im Allgemeinen ist der hier vorgestellte Ansatz analog zur Synthese von Isoxazolen und Isoxazolinen aus Aldoximen [29] . Die Synthese von Nitrilen, Isoxazolinen und Isoxazolen kann durch Elektrolyse über Nitriloxide als Schlüsselintermediate erreicht werden [30–34] . Diese Reaktionen werden seit den späten 1980er Jahren untersucht, als Shono et al.…”